CHEMICAL CONSTITUTION AND PHARMACOLOGICAL ACTION 415 



From these considerations it is at once clear that there is a link 

 between chemical constitution and pharmacodynamic a.ction, namely, 

 the distribution in the organism. In this we are dealing with a prin- 

 ciple which has long been known, and which, I might say, is almost 

 self-evident, but which nevertheless is clearly expounded in but 

 few text-books on therapeutics (see Stockvis, de Buck, and especially 

 H. Schulz). 



Unfortunately we have been satisfied with a mere theoretical 

 acknowledgment of this principle, and have practically made no 

 efforts to gain a deeper insight into the laws governing this distribu- 

 tion. This is esepcially true of tne new synthetic tendency, which 

 labors exclusively for symptomatic effects and leaves questions con- 

 cerning localization absolutely untouched. To my mind just this 

 neglect is to blame for the insufficient progress thus far made, and 

 I believe that new points of vantage can easily be gained if the 

 distributive views are given greater prominence. In this connection 

 I may call attention to the fact that through the application of the 

 principle of localization, which I have attempted, new and promising 

 paths have been opened up in the domain of bacteriology, although 

 this subject was already beginning to become barren under the sche- 

 matic application of the doctrines of immunity. 



To be sure it must be admitted that there are enormous difficulties 

 attending the determination of the distribution of chemical substances 

 with the necessary degree of precision. We are here confronted 

 with a problem whose solution is simple in only a few special cases. 

 These we shall discuss in a moment. In the great majority of 

 chemical compounds, however, only a combination of various methods 

 gives us any definite knowledge. 



Animal experiments, as such, do not give us complete informa- 

 tion concerning the distribution in the organism; they only mark 

 the regions most susceptible to the poison, and then usually only for 

 those systems, such as the nervous or muscular system, in which 

 disturbances of function are recognizable. The animal experiment, 

 however, furnishes but little information concerning the processes in 

 the vital parenchyma, for to these graphic or other ordinary physio- 

 logical methods are inapplicable. 



The assistance afforded by pure chemical analysis is very slight. 



is insufficient to destroy the powerful NH-NH, group of phenylhydrazin, or 

 the two amido groups of benzidin. 



